An apparatus and method are described to monitor the time of sound transmission in the blood stream of a patient, to use a linear relationship between compressibility and density for accurate and sensitive assessment of blood density changes, and to employ optical density for assessment of hematocrit changes due to dilution by saline, dialysate or therapeutic changes. Through appropriate clinical protocols, the density and hematocrit changes are used individually or in combined form to determine the plasma protein concentration, blood volume, change in blood volume, and microvascular pooling of the patient over time.
Hypotension and hypovolemia are common circulatory problems that occur during shock (Chien et al, American Journal of Physiology, 210:1411-1418), traumatic injury, dialysis (Amerling et al in Clinical Dialysis 3rd Edition, Appleton and Lang editors, 1995) and surgical interventions. A variety of disorders and injuries are related to the occurrence of hypotension (Daugirdas, Kidney International 39:233-246). Fluid loss related to burn injury or hemorrhage due to trauma is examples of situations where compensation for such loss is necessary. Infusing isotonic saline, plasma or other physiological solutions into the circulation until arterial pressure is elevated to normal is usually employed as the treatment. Although blood volume reduction correlates with reduction in arterial pressure under laboratory simulations of injury and anesthesia, actual occurrences of traumatic blood loss often show only slightly reduced arterial pressures due to the body's neural compensation mechanisms. Once these mechanisms reach their limits, arterial pressure can drop rapidly. The management of this subnormal arterial pressure is critical to survival; immediate restoration of arterial pressure after traumatic injury can cause more problems than allowing the pressure to remain subnormal. Rapid restoration of arterial pressure results in higher oxygen demand and the increase in blood flow may dislodge clots to cause stroke.
While the body's compensation mechanisms are important to survival, limitations exist in the ability to determine several factors including the volume of blood loss, the distribution of blood volume between the microcirculation and macrocirculation, the necessary volume for infusion, and whether overexpansion of the blood volume has occurred after infusion. Arterial pressure monitoring is unable to provide sufficient information to address these concerns. A need exists for precise monitoring of changes to blood volume and microvascular pooling in patients, particularly over extended time periods.
Beyond trauma and burn injury, a number of medical conditions require such precise monitoring of blood volume. Invasive surgery and dialysis are two common situations where monitoring blood volume changes provide important information related to the outcome of the surgery and dialysis. For example, about 30% of patients undergoing dialysis in the United States will experience hypotension and, occasionally, circulatory shock. Milder symptoms include muscle cramping and lightheadedness. These dialysis related side effects are implicated in reduced dialysis efficacy.
Dialysis and systems for dialysis are well known in the art. These work by extracting a significant fraction of fluid from the circulating blood. Compensation for this reduction in blood volume normally occurs through fluid restituted from the tissue. The activation of the microcirculation by hemodialysis leads to pooling of blood in the microcirculation affecting a low venous return, poor cardiac filling, lowered cardiac output and then hypotension. For patients undergoing a well-controlled fluid removal, these cardiovascular changes and hypovolemia are the reason for hypotension development during the course of hemodialysis. Using saline or dialysate dilution, we can monitor the change in blood volume over times, for example every half hour. A continuous change in blood density can be analyzed and microvascular pooling within the circulation can be determined. These parameters can be used by physicians to carefully monitor the cardiovascular changes that are responsible for the development of hypotension in dialysis patients.
When patients undergo hemodialysis or are subject to trauma or burns, there is significant exchange of fluid and protein between the tissue and blood compartment. These exchanges will alter the plasma protein concentration. Consequently an on-line system capable of monitoring changes in plasma protein concentration will be valuable to the physician in selecting an appropriate fluid therapy to compensate for the loss of plasma and/or plasma protein. Currently no system can assess on-line and clinically monitor plasma protein concentration.
The use of sound velocity measurements in blood to assess blood volume has been attempted and described previously. Krivitski, in U.S. Pat. Nos. 5,453,576 and 5,685,989 describes an apparatus and method for measuring several hemodynamic parameters by using a sound velocity sensor. The information contained in the '576 and the '989 patent is incorporated by reference as though cited in its entirety. The technique described uses a linear approximation of a non-linear relationship between the sound velocity and the density of the blood. This approximation introduces additional error into the volume computation, which limits the accuracy of the system. Further, the '576 patent is limited to large variations in sound velocity which make it inaccurate to assess blood volume.
The system patented by Schneditz in U.S. Pat. No. 5,830,365 also utilizes sound velocity for the measurement of total protein concentration, and then the blood volume by altering the dialyzer to run at a different ultrafiltrate extraction rate. These two methods are limited to large variations in sound velocity and the requirement of no blood pooling to the microcirculation.
Several other devices exist which are used to monitor blood volume or blood parameter changes. These include the Know-Recirc™ hematocrit measurement device produced by H&H Control Systems (Jackson, M S) and described in U.S. Pat. No. 5,312,550 and an optical device marketed under the Crit-Line® platform and the Transcutaneous Access Flow device by HemaMetrics Corporation (Boston, Mass.) described in U.S. Pat. Nos. 5,499,627 and 6,117,099. These devices continuously monitor the change in hematocrit over a dialysis session. Increases in hematocrit over the session are interpreted as a decrease in plasma volume thereby theoretically providing a mechanism for monitoring blood volume changes. This method does not account for the Fahraeus effect where microvascular pooling of blood can result in an increase in hematocrit. By not correcting for microvascular pooling, blood volume changes estimated by this device are off by a factor of two or more. Again, sensitivity of this device is limited and can cause incorrect diagnoses or treatments. Daugirdas (American J. Kidney Disease, 38:S11-S17, 2001) commented that none of these hematocrit approaches are successful because the conclusion from the measured hematocrits exhibits considerable interpatient and intrapatient variability. A similar problem exists in the work of Polaschegg in U.S. Pat. No. 5,230,341. Correction for microvascular pooling and sensitivity are deficient in the '341 patent and incorrect results on the projected blood volume occur leading to potentially harmful treatments.